A mass spectrometry (MS) system in general includes an ion source for ionizing molecules of a sample of interest, followed by one or more ion processing devices providing various functions, followed by a mass analyzer for separating ions based on their differing mass-to-charge ratios (or m/z ratios, or more simply “masses”), followed by an ion detector at which the mass-sorted ions arrive. An MS analysis produces a mass spectrum, which is a series of peaks indicative of the relative abundances of detected ions as a function of their m/z ratios. Mass spectrometers are commonly used to determine the chemical composition of mixtures by precise measurement of the mass-to-charge ratio of the constituent molecular ions.
One particular type of mass spectrometer is a time-of-flight mass spectrometer (TOF-MS), which is utilized for molecular and elemental identification within a variety of disciplines ranging from medicine, biological research, environmental monitoring, chemical manufacturing, energy, and forensics. Time-of-flight mass spectrometry (TOF-MS) offers a powerful combination of mass resolution, accuracy, speed, and mass range which together make the technique well-suited for the analytical challenges presented by these fields. TOF-MS utilizes a high-resolution mass analyzer (TOF analyzer) in the form of a flight tube, which encloses a space that is electric field-free except for localized fields imparted by devices in the flight tube such as an ion mirror. An ion accelerator (or pulser) injects ions in pulses (or packets) into the flight tube. Ions of differing masses travel at different velocities through the flight tube and thus separate (spread out) according to their differing masses before arriving at the ion detector, enabling mass resolution based on time-of-flight. In a typical TOF-MS, ions travel along a drift direction through one or more gas-filled ion guides, and one or more beam-limiting apertures operating in a collision-free environment, and into the pulsed ion accelerator. In an orthogonal acceleration TOF-MS (oaTOF-MS), the ion accelerator receives the ions along the drift direction and injects the ions along an acceleration direction orthogonal to the drift direction. The flight tube may include one or more ion mirrors (or “reflectrons”) that increase the length of the ion flight path and provide certain advantages.
In TOF-MS, chemical composition is determined by accurately measuring the masses of individual ions drawn from the sample. The critical mass measurement stage is realized by measuring the time elapsed as ions travel from an ion accelerator through a known path length. Ions end their flight on a fast ion detector at which a single ion is transformed into a nanosecond-scale electronic signal, which is digitized with a high speed data acquisition system. The inherent simplicity and speed of this process translates into multiple analytical advantages for the end user. Because TOF-MS is able to gather a complete mass spectrum for each firing of the ion accelerator, it is particularly well-suited for tandem mass spectrometry (MS/MS) in which the fragmentation spectrum associated with a particular parent ion mass is measured.
Orthogonal-acceleration TOF-MS instruments have a primary ion beam that travels at low energy (10-50 eV) in a direction known as the drift direction, and an ion accelerator that accelerates the ions in an acceleration direction orthogonal to the drift direction. A well-known problem attending a TOF-MS instrument is that its duty cycle is inherently inefficient. The origin of the duty-cycle inefficiency lies in the fact that the ion accelerator is inherently pulsed while most mass spectrometer ion sources are continuous. The mass analysis time, and hence the firing period of the ion accelerator, is equal to the time-of-flight for the largest mass measured (i.e., the longest flight time associated with any ion packet injected into the flight tube) and is generally much longer than the time it takes to fill the ion accelerator. Consequently, ions that enter the ion accelerator more than one fill-time before the next firing of the ion accelerator are lost. The duty cycle is the portion of ions of the primary ion beam that is accelerated and transmitted through the ion accelerator into the TOF mass analyzer. Duty cycle is equal to the ratio of the ion accelerator fill-time to the firing period and depends on ion mass.
Known methods for improving duty cycle loss can be divided into two classes. The first class of methods involves trapping the ions before the ion accelerator to create a pulsed beam from the original continuous beam. The trapping methods suffer from difficulties associated with ejecting the ions from the trap with appropriate timing, particularly when ion-ion repulsion is considered, as well as the ion loss associated with the mass separation between the ion trap and the ion accelerator. The second class of methods employ what is known as “multi-pulsing” or “multiplexing” wherein the ion accelerator is fired to inject a new ion packet before the previous ion packet has completed its flight path in the mass analyzer. Multi-pulsing results in more than one ion packet being present in the flight tube at the same time, which can lead to overlapping between successive ion packets, with the slower ions of one ion packet being overtaken by the faster ions of a subsequently fired ion packet. Multi-pulsing thus often necessitates reconstruction of a meaningful mass spectrum from the convoluted raw detector data, which requires some means of determining from which accelerator firing each detected ion originates. Known multi-pulsing methods use slight variations in pulse firing time (dithering) to encode the firing number. Signal processing algorithms are then used to reconstruct the actual mass spectrum based on the knowledge of the encoding scheme. The algorithms rely on statistical inference and are subject to error due to imperfect reconstruction, and often require a large amount of computer processing.
Therefore, there is a need for improving the duty cycle in TOF-MS while avoiding the problems associated with the known, conventional approaches.